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探索成簇规律间隔短回文重复序列-CRISPR相关蛋白9（CRISPR-Cas9）作为癌症治疗手段的研究：一项范围综述

Exploring Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-Associated Protein 9 (CRISPR-Cas9) as a Therapeutic Modality for Cancer: A Scoping Review.

作者信息

Balasubramanian Abirami, Veluswami Keerthana, Rao Sudipta, Aggarwal Shailesh, Mani Sweatha

机构信息

Internal Medicine, Stanley Medical College, Chennai, IND.

Internal Medicine, Jagadguru Sri Shivarathreeshwara (JSS) Medical College, Mysore, IND.

出版信息

Cureus. 2024 Jul 11;16(7):e64324. doi: 10.7759/cureus.64324. eCollection 2024 Jul.

DOI:10.7759/cureus.64324
PMID:39130943
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11316854/
Abstract

The global burden of cancer and the limitations of conventional therapies highlight the potential of clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR-Cas9) in reshaping cancer treatment paradigms. In this review, we have investigated the mechanism of CRISPR, an adaptive immune system in bacteria that enables highly precise gene editing at the molecular level. This versatile tool demonstrates its efficacy in human cancer therapy through gene knockout, metabolic disruption, base editing, screening, and immunotherapy enhancement without affecting normal bodily domains. Despite its superiority over other nucleases like zinc-finger nucleases and transcription activator-like effector nucleases, hurdles such as off-target effects, inefficient delivery of the system to target cells, the emergence of escapers, and the ethical debate surrounding genome editing are discussed. In this article, we have reviewed the promising approaches of CRISPR-Cas9 in cancer treatment while exploring the underlying mechanism, advantages, and associated challenges.

摘要

癌症的全球负担以及传统疗法的局限性凸显了成簇规律间隔短回文重复序列-CRISPR相关蛋白9（CRISPR-Cas9）在重塑癌症治疗模式方面的潜力。在本综述中，我们研究了CRISPR的机制，它是细菌中的一种适应性免疫系统，能够在分子水平上实现高度精确的基因编辑。这种多功能工具通过基因敲除、代谢破坏、碱基编辑、筛选和增强免疫疗法，在不影响正常身体区域的情况下，证明了其在人类癌症治疗中的有效性。尽管它比其他核酸酶如锌指核酸酶和转录激活样效应核酸酶具有优势，但仍讨论了诸如脱靶效应、系统向靶细胞递送效率低下、逃逸者的出现以及围绕基因组编辑的伦理辩论等障碍。在本文中，我们回顾了CRISPR-Cas9在癌症治疗中的有前景的方法，同时探讨了其潜在机制、优势和相关挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/72d332797c7d/cureus-0016-00000064324-i12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/8cd087043cef/cureus-0016-00000064324-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/94e544543f24/cureus-0016-00000064324-i02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/ae2e8ab7cf68/cureus-0016-00000064324-i03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/158d49c159ad/cureus-0016-00000064324-i04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/e760eb41fbc6/cureus-0016-00000064324-i05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/8d0860162d7f/cureus-0016-00000064324-i06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/2e34a39ad0ca/cureus-0016-00000064324-i07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/08ab18eb726c/cureus-0016-00000064324-i08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/fa2e47435da4/cureus-0016-00000064324-i09.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/bcfe359df66f/cureus-0016-00000064324-i10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/9b307ac2adcc/cureus-0016-00000064324-i11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/72d332797c7d/cureus-0016-00000064324-i12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/8cd087043cef/cureus-0016-00000064324-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/94e544543f24/cureus-0016-00000064324-i02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/ae2e8ab7cf68/cureus-0016-00000064324-i03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/158d49c159ad/cureus-0016-00000064324-i04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/e760eb41fbc6/cureus-0016-00000064324-i05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/8d0860162d7f/cureus-0016-00000064324-i06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/2e34a39ad0ca/cureus-0016-00000064324-i07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/08ab18eb726c/cureus-0016-00000064324-i08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/fa2e47435da4/cureus-0016-00000064324-i09.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/bcfe359df66f/cureus-0016-00000064324-i10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/9b307ac2adcc/cureus-0016-00000064324-i11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef94/11316854/72d332797c7d/cureus-0016-00000064324-i12.jpg

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Front Pharmacol. 2023 Nov 21;14:1284610. doi: 10.3389/fphar.2023.1284610. eCollection 2023.
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Deletion of the inhibitory co-receptor CTLA-4 enhances and invigorates chimeric antigen receptor T cells.抑制性共受体 CTLA-4 的缺失增强并激活嵌合抗原受体 T 细胞。
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Postoperative recurrence in locally advanced rectal cancer: how does neoadjuvant treatment affect recurrence pattern?
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CRISPR/Cas9: A Powerful Strategy to Improve CAR-T Cell Persistence.CRISPR/Cas9：提高 CAR-T 细胞持久性的有力策略。
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CRISPR Cas12a-mediated amplification-free digital DNA assay improves the diagnosis and surveillance of Nasopharyngeal carcinoma.CRISPR Cas12a 介导的无扩增数字 DNA 检测可提高鼻咽癌的诊断和监测。
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